The goal of these studies is to increase understanding of the pathogenesis of parasitic diseases and to improve their diagnostic, therapeutic and preventative measures. Investigations have been carried out in patients both at NIH and in the endemic areas of Guatemala (onchocerciasis), India (filariasis, kala azar), Mexico (leishmaniasis), and Sudan (schistosomiasis). Diagnostic refinements have been made with immunoassays for lymphatic filariasis, loiasis, onchocerciasis and strongyloidiasis and with clinical measures (ultrasonography) for schistosomal liver fibrosis. Studies on pathogenesis have shown that differential immune responsiveness is correlated with lymphatic filariasis pathology (IgG3) and that local IgG antibodies and infiltrating T suppressor/cytotoxic cells are associated with the eye lesions of onchocerciasis. Antigen-specific immune unresponsiveness is characteristic of both kala azar and filarial infections, but the mechanisms underlying this immunologic unresponsiveness appear different. Therapeutic studies with ivermectin have shown it to be at least as effective and safe at low dosages in bancroftian filariasis as the currently used drug diethylcarbamazine and to be the only drug demonstrated effective in mansonellosis. Against strongyloides its curative effect has been only temporary in some individuals. Collaborative studies of a recombinant sporozoite vaccine for falciparum malaria in human volunteers has shown a protective effect in only one of six vaccines. The lack of good booster responses suggests that modifications will be necessary for this prototype vaccine.